Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head

Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head
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髋关节软骨的蛋白质组学分析鉴定了与股骨头坏死相关的差异表达蛋白质

DOI:
10.1016/j.joca.2021.04.005
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发表时间:
2021-06-17
影响因子:
7
通讯作者:
Liu, R.
Liu, R.
中科院分区:
医学2区
文献类型:
--
作者:
Song, J.;Wu, J.;Liu, R.

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目的:软骨下骨坏死伴发的软骨退行性变在股骨头坏死的发生发展中起重要作用。为了更好地了解ONFH软骨退化的分子基础,我们比较了ONFH软骨和骨折对照组的蛋白质组图谱。设计:收集16例股骨颈骨折患者和16例正常对照的髋关节软骨标本。蛋白质组学分析采用串联质量标签定量技术。通过基因本体论(GO)分析、KEGG途径分析和蛋白质-蛋白质相互作用分析,研究改变的蛋白质和生物途径的功能。通过免疫印迹(WB)和免疫组织化学(IHC)验证差异表达的蛋白质,包括α-2-HS糖蛋白(AHSG)和细胞因子样蛋白1(Cytl1)。结果:共鉴定出303个差异表达蛋白质,其中72个表达上调,231个表达下调。在ONFH软骨中,胶原周转、糖胺多糖的生物合成、代谢途径、补体和凝血级联均显著改变。WB和IHC证实ONFH软骨中AHSG表达增加,Cytl1表达降低。结论:我们的结果揭示了蛋白表达改变在ONFH的发生发展中的意义,并为ONFH软骨退化的发病机制研究提供了新的线索。(C)2021年国际骨关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control. Design: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC). Results: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage. Conclusions: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH. (c) 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.